The long term objective of this project is a better understanding of the role of genetic and environmental factors in human behavioral/neurological disorders through the study of the specific disorder Tourette syndrome (TS). Until recently, Tourette syndrome was considered a very rare neuropsychiatric disorder. However, a greater understanding of the symptomology of TS, with the resultant decrease in misdiagnosis, has led to a realization that TS is much more common than had ever been considered. Its frequency and its effect on those afflicted makes TS a major public health problem. Understanding the genetics of TS will be of direct benefit to patients concerned about recurrence in their families and will also be helpful in clarifying the role of environmental factors; ultimately, clarifying the genetics of TS may elucidate its pathogenesis. As part of the ongoing family study designed to study the genetics of TS, data on 37 families have been collected and partially analyzed. Because preliminary analyses suggest a relationship between TS and several other disorders, we now propose to at least double the size of our sample by studying an additional 50-60 families. We will collect, by direct structured inverview of all first degree relatives of the probands, data designed to confirm and extend the initial findings that chronic tic disorder and obsessive-compulsive disorder are related, possibly milder, forms of TS. About 15 of these families will be studied intensively for genetic linkage including, in addition to standard polymorphic typing, typing for new polymorphic DNA markers identified using restriction enzyme techniques. The linkage data will increase our ability to isolate and characterize any genetic component. Data from both of these samples will be helpful in identifying possible etiological heterogeneities, and to confirm or reject hypotheses of cultural transmission. Concomitantly with the collection and analyses of data on TS families, we will pursue development of new analytic methods appropriate for disorders like Tourette syndrome.